Antimicrobial Resistance to Lefamulin and Its Role in CABP Management

According to a recent review, lefamulin demonstrates consistently low in vitro resistance among principal CABP pathogens.

Pooled in vitro studies report Streptococcus pneumoniae resistance of 0%–2.6% and Haemophilus influenzae resistance of 0%–2.4% from aggregated surveillance MIC distributions. These pooled MIC data underscore lefamulin's retained activity against common respiratory isolates.

Staphylococcus aureus, including MRSA, shows resistance of 0%–4.3%; overall MIC distributions for S. pneumoniae, H. influenzae, and S. aureus indicate high susceptibility to lefamulin. Lefamulin, a pleuromutilin, binds the peptidyl transferase center of the 50S ribosomal subunit—a mechanism that aligns with a low rate of cross-resistance and broad activity compared with common beta-lactam and macrolide resistance patterns.

Clinically, these low resistance rates support considering lefamulin as an empirical option for CABP when first-line agents are unsuitable—eg, beta-lactam allergy, high local macrolide resistance, or elevated MRSA risk. This resistance profile should inform initial management while preserving local stewardship judgment. Continued local susceptibility testing and routine antimicrobial surveillance are necessary to detect emergent resistance and guide local policy.